Oral keratinocytes act as the major barrier to physical, microbial, and chemical agents that may cause local cell injury. They are related with the proinflammatory process through the production of cytokines either constitutively or after a variety of stimuli. Consequently, oral keratinocytes may potentially participate in controlling oral infections through an inflammatory process. This process involves different interleukins, such as IL-1β and IL-18. Oral keratinocytes express a variety of differentiation markers, the expression of which comprises calcium-induced changes in the transcription of target genes. Oral keratinocytes share major structural and functional features with the well-characterized dermal keratinocyte. Human Oral Keratinocytes are useful tools to study basic keratinocyte biology, as well as, processes of immortalization and malignant transformation.